Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.1.53 (
sialidase
)
2,694
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We investigated the cellular and molecular mechanisms underlying arrhythmias in heart failure. A genetically engineered mouse lacking the expression of the muscle LIM protein (
MLP
-/-) was used in this study as a model of heart failure. We used electrocardiography and patch clamp techniques to examine the electrophysiological properties of
MLP
-/- hearts. We found that
MLP
-/- myocytes had smaller Na+ currents with altered voltage dependencies of activation and inactivation and slower rates of inactivation than control myocytes. These changes in Na+ currents contributed to longer action potentials and to a higher probability of early afterdepolarizations in
MLP
-/- than in control myocytes. Western blot analysis suggested that the smaller Na+ current in
MLP
-/- myocytes resulted from a reduction in Na+ channel protein. Interestingly, the blots also revealed that the alpha-subunit of the Na+ channel from the
MLP
-/- heart had a lower average molecular weight than in the control heart. Treating control myocytes with the
sialidase
neuraminidase mimicked the changes in voltage dependence and rate of inactivation of Na+ currents observed in
MLP
-/- myocytes. Neuraminidase had no effect on
MLP
-/- cells thus suggesting that Na+ channels in these cells were sialic acid-deficient. We conclude that deficient glycosylation of Na+ channel contributes to Na+ current-dependent arrhythmogenesis in heart failure.
...
PMID:Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. 1136 78
